4. How can bacteria become resistant to biocides or antibiotics?

4.3 Which resistance mechanisms are common to both biocides and antibiotics?

4.1 How can bacteria become resistant to biocides?

Bacteria become
resistant to biocide
exposure when they are able to limit their internal
concentration of active biocide to harmless levels. Bacteria can
do this by a number of methods and may combine several.

For instance, some
bacteria become
resistant by changing the
structure of their
cell envelope
so that it lets in smaller amounts of
biocides. This is
particularly the case of bacteria that grow as
biofilms attached to
surfaces. The outer layers of biofilms are considerably less
permeable than those of free bacteria, and this could lead them
to be much less easily affected by biocides and
antibiotics.

Some bacteria become more
tolerant to
biocides by activating a
system that “pumps out”
toxic compounds generally
termed efflux pump. This reduces the efficacy
of biocides.

Some bacteria use
enzymes to cause chemical
changes in biocides and to
degrade them so that they are less effective,
but it is not clear whether this mechanism is relevant for the
high concentrations of biocides used in practice.Some bacteria
use enzymes to cause chemical changes in biocides and to degrade
them so that they are less effective, but it is not clear
whether this mechanism is relevant for the high concentrations
of biocides used in practice.

Bacteria can
modify the parts of their structure that
biocides attach to and
attack. However, there are many different sites that biocides
can target so modifying one of these does not have a large
effect on increased
resistance.

Bacteria that could
previously be controlled by a biocide can develop
resistance by
acquiring resistance genes
and this is a serious cause for concern. In some cases, exposure
to a low biocide concentration leads to genetic changes that
make the bacteria
resistant to several
unrelated compounds, but the mechanism for this is
unknown.

Recent studies have demonstrated that some
biocides are able to
activate several genes that
are involved in the control of
resistance mechanisms
affecting the activity of biocides and
antibiotics.

Sometimes bacteria become
resistant once they reach
sufficiently high numbers. Bacteria secrete certain “signal”
molecules that other
bacteria can detect. Once bacteria detect enough of these from
neighbouring bacteria, the whole colony activates specific
genetic cascades involved in the formation of
biofilms. This mechanism
is involved in the development of
resistance to
biocides and
antibiotics but more
research is needed in this field.
More...

Bacteria may be
“insusceptible” or intrinsically
resistant to an
antibiotic because they
have no sites that the molecule can attack, because the envelope
does not let the antibiotic in, because some efflux pumps expel
the antibiotic, or because the bacteria produce
enzymes that destroy
it.

An increasing and ongoing concern are
bacterial strains that
become resistant by
mutation, by changing their gene expression or by transfer of resistancegenes from other
bacteria. The transfer of
genes can take place in different ways but usually involves
genes that can move between different parts of the
genome. Some of these
acquired genes enable the
bacterium to destroy the
antibiotic or to expel it
and others change the parts of the bacteria that
antibiotics attack. There
are three possible mechanisms:

Bacteria can make
their membrane less permeable to the
antibiotic or “pump
out” any antibiotic from the
cell before it starts
to act by producing an efflux pump.

Bacteria can attack the antibiotic (alter the
structure) and make it ineffective by producing detoxifying
enzymes.

Bacteria can protect or modify the parts of their
structure that
antibiotics attack
(target mutation) or can produce decoys that antibiotics
attack instead of the real target sites.

“Multi-drug resistantbacteria” that become
simultaneously resistant to different classes of
antibiotics are a cause for
serious concern in hospitals, where they are commonly found.
They mainly act by pumping out any compounds harmful to them so
that their concentration inside the bacteria becomes harmless in
addition to other
resistance mechanisms
including target mutation or detoxifying
enzymes.

Once resistantbacteria emerge, using
antibiotics can help
resistant strains thrive by killing other strains so that
bacteria with resistancegenes can grow and
reproduce without competition from other strains. These bacteria
can also transfer their resistance genes to other bacteria of
similar or different
species.
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4.3 Which resistance mechanisms are common to both biocides and antibiotics?

There are many similarities in the ways that
biocides and
antibiotics penetrate
bacteria and work. Both
diffuse into bacteria, they can modify or destroy the
bacterial membrane, i.e.
the layer that encloses the
bacterium, and can disrupt
key steps in bacterial chemical reactions. Therefore, some
bacterial mechanisms of defence are effective against both
antibiotics and biocides such as the decrease of membrane
permeability that reduce the uptake of active
molecules, or the
production of efflux pumps that expel
antibiotic and biocide
molecules.

Genes that confer
resistance to
antibiotics can also be
involved in biocide resistance such as efflux pump genes, so
bacteria that acquire
resistance genes sometimes become
resistant to both types of
antimicrobials at the same
time. In other cases, genes that confer resistance to different
antimicrobial products
(such as beta-lactams and quaternary ammonium products) are very
close to each other in a same genetic element (plasmid,
transposon, etc) transferable from one
bacterium to another. As a
result, when this genetic element passes from one bacteria to
another, both types of resistance genes (to antibiotics and to
biocides) are transmitted
together.

This raises concerns over the indiscriminate and often
inappropriate use of
biocides in situations
where they are unnecessary, because it can contribute to the
development of resistance
mechanisms. This is especially important in cases where
potentially harmful
bacteria, such as those
found in hospitals, are exposed to biocides.
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